This invention relates to a process for oxidizing a penicillin to a penicillin sulfoxide. Depending upon the position of the oxygen of the sulfoxide moiety, penicillin sulfoxides can exist in either the .alpha.- or the .beta.- form. These can be depicted as follows: ##STR1##
The literature recognizes several methods for oxidizing a penicillin to its penicillin sulfoxide. In most instances, these methods achieve production of the .beta.-sulfoxide with little or no production of the .alpha.-sulfoxide. The typical recognized oxidation methods can be grouped as follows:
(1) Use of peracids
These methods involve treatment of the penicillin with a peracid, such as m-chloroperbenzoic acid or peracetic acid. The peracetic acid can be formed in situ from a mixture of hydrogen peroxide and acetic acid. In every case, the only sulfoxide which is formed has the .beta.-configuration. These methods are described in publications such as, for example, Cooper et al., J. Am. Chem. Soc. 91, 1408 (1969), and Barton et al., J. Am. Chem. Soc. 91, 1529 (1969).
(2) Use of hydrogen peroxide
This method achieves only a very low level of conversion and produces exclusively the .beta.-sulfoxide. The extent of conversion can be potentiated by incorporation of a catalyst, for example, sodium tungstate. This method is referred to in Japanese Pat. No. 91087/73.
(3) Use of ozone
A penicillin can be oxidized to a mixture of the .alpha.- and .beta.-sulfoxides by treatment with ozone. Although this method permits production of the .alpha.-sulfoxide in addition to the .beta.-sulfoxide, it suffers by reason of the fact that, in order to achieve any substantial .alpha.-sulfoxide formation, a very dilute aqueous system is required. This precludes any practical application of the ozone oxidation process in production of .alpha.-sulfoxide. Moreover, the .alpha.-sulfoxide which is recovered from the ozone process is a relatively impure and amorphous material which requires additional crystallization treatments with attendant product loss. Spry, J. Am. Chem. Soc., 92, 5006 (1970) describes this method.
A process has now been discovered which permits oxidation of penicillins to produce penicillin sulfoxides in highly pure form, and, in many cases, substantial quantities of the penicillin .alpha.-sulfoxide. It is to such a process that this invention is directed.